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Original Research

The therapeutic efficacy of propranolol in children with recurrent primary epistaxis

, , , , , , & show all
Pages 127-129 | Published online: 01 Mar 2013

Abstract

We hypothesized that some characteristics of beta-blockers, including negative inotropic, peripheral vasoconstrictor, and antiangiogenic effects, might be potentially useful in treating children with epistaxis. From June 2010 to March 2012, a total of seven children with recurrent primary epistaxis resistant to conventional management were observed at our institution. An overall effectiveness of propranolol was noted in all seven children when given a dose of 1.5–2 mg/kg/day (divided into three doses) as a second line therapy for terminating epistaxis. Based on our first experience, we believe that propranolol could be a favorable treatment option for patients with primary epistaxis.

Introduction

Epistaxis is a common medical problem in the pediatric population, and may generate considerable distress and anxiety among children and their parents. Although in most cases it is mild and self-limiting, a proportion of childhood epistaxis is massive, recurrent, or resistant to conventional management.Citation1

At this date, there are still no relevant clinical data concerning the usefulness of nonselective beta-blockers in treating epistaxis.Citation2 However their antagonistic beta-1, and beta-2 adrenoceptor effects, together with their recently discovered antiangiogenic effect, suggests that nonselective beta-blockers have potentially useful hemostatic abilities.Citation2Citation5

We present a case series of seven children with primary recurrent epistaxis, resistant to conventional management, who were treated with propranolol as a second line agent.

Methods

From June 2011 to March 2012, we saw seven children who were previously diagnosed to have a recurrent (at least one episode per week) and protracted (more than one month of duration) primary epistaxis and were previously unsuccessfully treated with standard therapy (topical antiseptic cream and local vasoconstrictors). Prior to referral to our institution, all children underwent rigid nasal endoscope examinations performed by the same physician (BM) and those that were found to have a specific intranasal pathology (other than prominent vessels on the nasal septum, crusting, or irritation) were excluded from the study. The study was approved by the local ethics committee of the Faculty of Medicine, University of Nis, Serbia No 01-244-2.

The children were started on propranolol if there were no other secondary causes of epistaxis, no history of receiving antiplatelet and/or anticoagulant therapy, and no bradycardia, hypotension, or bronchospasm prior to treatment initiation. As part of the initial evaluation, we performed complete blood counts as well as official blood pressure measurements on all our patients.

The dose of propranolol was initiated on an outpatient basis and arbitrarily set at 1.5–2 mg/kg/day, divided into three doses. The treatment duration was also arbitrarily limited to at least two weeks and maximum one month depending on patients’ compliance. All the children’s families also received standardized instructions regarding home heart rate monitoring, fasting, and signs of hypoglycemia such as sweating, shaking, anxiety, lethargy, hypothermia, or seizures. Occurrence of only one episode of epistaxis within the first month after the last dose of propranolol was considered as a treatment failure. All patients were followed up for six months.

Results

From June 2009 to March 2011, we saw a total of seven children (five boys and two girls, mean age 7.43 ± 2.8 years, age range 4–12 years) who fulfilled our inclusion criteria.

The overall effectiveness of propranolol for terminating epistaxis was successful in all seven children and we did not have any side effects of the treatment. During six months follow-up, only one child (Case 5) had recurrence of epistaxis. His first subsequent bleeding episode occurred for the first time on day 43 after the propranolol initiation and was in the form of minor, self-limiting nose bleeding. During the subsequent follow up period, he had only rare, once or twice a month or even bimonthly episodes of epistaxis. Of note is that prior to referral to our institution, he had almost daily massive nosebleeds, leading him to develop severe hypochromic anemia. For that reason, he also underwent repeated nasal packing to terminate the bleeding and he was considered for transfusion. On the other hand, all other laboratory investigations that were performed (bleeding time, prothrombin time, activated partial thromboplastin time, thrombin time, platelet aggregation, factors I, II, VIII. IX and von Willebrand factor, as well as thrombocyte aggregation, col/ADP, col/epi, and D dimer) revealed normal findings.

Clinical data for all seven children are summarized in .

Table 1 Clinical data of all children included in the study

Discussion

At this date, there are no relevant clinical data concerning the usefulness of propranolol for treating children with epistaxis.Citation1,Citation2 This case series provides support for the use of propranolol as a potential treatment option for children with epistaxis.

We would like to emphasize a few important features of propranolol that are potentially hemostatic. By antagonizing beta-1 adrenoceptors, propranolol lowers stroke volume and blood pressure, both of which are frequently elevated in patients with epistaxis.Citation2 This possibly adverse effect, associated with â2-adrenergic receptor antagonist activity (peripheral vasoconstriction), is a potentially desirable feature in epistaxis, as well as in a number of other bleeding disorders without signs of hemorrhagic shock.Citation2,Citation3,Citation6,Citation7

Recent data also indicate a strong antiangiogenic effect of propranolol.Citation8,Citation9 Propranolol was shown to have a direct effect on tumor angiogenesis, and has recently been introduced as a novel treatment modality for proliferating hemangiomas and some other solid neoplastic proliferations.Citation10 Vasoconstriction, decreased expression of basic fibroblast growth factor, matrix metalloproteinase, and vascular endothelial growth factor, and up-regulation of apoptosis of capillary endothelial cells are some of the pathophysiological mechanisms responsible for the antiangiogenic effect of propranolol.Citation11 Likewise, propranolol might be potentially useful in children with primary epistaxis. After biopsies of the nasal septal mucosa were taken from five children with recurrent epistaxis undergoing nasal cautery, Montague et al found prominent thin-walled arterioles and capillaries with a surrounding inflammatory infiltrate, with no evidence of venous varicosities or arterial microaneurysms. They postulated a mechanism for septal neovascularisation due to chronic low-grade inflammation, as a cause for recurrent epistaxis in children.Citation12 Of note is that four of the seven of our patients had prominent vessels of the nasal septum.

Recently, the vascular endothelial growth factor inhibitor bevacizumab has shown promise as a medical treatment for epistaxis related to hereditary hemorrhagic telangiectasia. At this point, it is of interest to note the results of experimental study by Albinana et al,Citation13 who suggested the local administration of propranolol in the nose mucosa as a potential therapeutic option to control epistaxis in patients with hereditary hemorrhagic telangiectasia, as well as the results of clinical study by Olitsky,Citation14 who suggested topical timolol for the same indication. In our opinion, concerning its lower risk of adverse effects, timolol might also be a rational therapeutic option for children with recurrent epistaxis.

The final possible explanation for the therapeutic effect of propranolol might be related to its potential indirect alpha-1 agonist effect, indirectly provoking systemic veins vasoconstriction.Citation5,Citation15 We are of the opinion that all these outlined effects are potentially useful in patients with epistaxis and we suggest that this treatment strategy is highly rational in this indication. However, further prospective studies involving large samples and stricter inclusion criteria (eg, nasal cultures) are required to confirm our results.

Acknowledgments

This work has been supported by the Ministry of Science and Technology of the Republic of Serbia by grant No 175092.

Disclosure

The authors report no conflicts of interest in this work.

References

  • Brown NJ Berkowitz RG Epistaxis in healthy children requiring hospital admission Int J Pediatr Otorhinolaryngol 2004 68 9 1181 1184 15302149
  • Melia L McGarry GW Epistaxis: update on management Curr Opin Otolaryngol Head Neck Surg 2011 19 1 30 35 21150620
  • El-Shabrawi M Hassanin F Propranolol safety profile in children Curr Drug Saf 2011 6 4 259 266 22129321
  • Hampton JR Choosing the right beta-blocker. A guide to selection Drugs 1994 48 4 549 568 7528129
  • Young R Glennon RA S(-)Propranolol as a discriminative stimulus and its comparison to the stimulus effects of cocaine in rats Psychopharmacology 2009 203 2 369 382 18795268
  • Scheibe M Wüstenberg EG Hüttenbrink KB Zahnert T Hummel T Studies on the effects of ice collars on nasal blood volume using optical rhinometry Am J Rhinol 2006 20 4 394 396 16955766
  • Dagher L Burroughs A Variceal bleeding and portal hypertensive gastropathy Eur J Gastroenterol Hepatol 2001 13 1 81 88 11204818
  • Léauté-Labrèze C Dumas de la Roque E Hubiche T Boralevi F Thambo JB Taïeb A Propranolol for severe hemangiomas of infancy N Engl J Med 2008 12 358 24 2649 2651 18550886
  • Annabia B Lachambre MP Plouffe K Moumdjian R Béliveau R Propranolol adrenergic blockade inhibits human brain endothelial cells tubulogenesis and matrix metalloproteinase-9 secretion Pharmacol Res 2009 60 5 438 445 19467330
  • Lamy S Lachambre MP Lord-Dufour S Beliveau R Propranolol suppresses angiogenesis in vitro: inhibition of proliferation, migration, and differentiation of endothelial cells Vascul Pharmacol 2010 53 5–6 200 208 20732454
  • Pasquier E Ciccolini J Carre M Propranolol potentiates the anti-angiogenic effects and anti-tumor efficacy of chemotherapy agents: implication in breast cancer treatment Oncotarget 2011 2 10 797 809 22006582
  • Montague ML Whymark A Howatson A Kubba H The pathology of visible blood vessels on the nasal septum in children with epistaxis Int J Pediatr Otorhinolaryngol 2011 75 8 1032 1034 21676473
  • Albinana V Recio-Poveda L Zarrabeitia R Bernabéu C Botella LM Propranolol as antiangiogenic candidate for the therapy of hereditary haemorrhagic telangiectasia Thromb Haemost 2012 108 41 53 22552254
  • Olitsky SE Topical timolol for the treatment of epistaxis in hereditary hemorrhagic telangiectasia Am J Otolaryngol 2012 33 375 376 22079094
  • Sloand EM Thompson BT Propranolol-induced pulmonary edema and shock in a patient with pheochromocytoma Arch Intern Med 1984 144 1 173 174 6691755